title: The archaic roles of the amphioxus NF-κB/IκB complex in innate immune responses.
abstract: NF-κB transcription factors play important roles in immune responses and the development of the immune system. Many aspects of NF-κB signaling differ significantly among distinct species, although many similarities in signaling exist in flies and humans. Thus, to understand the functional refinement of the NF-κB cascade from invertebrates to vertebrates, the Rel and NF-κB proteins, identified as bbtRel and bbtp105, were characterized in a basal chordate amphioxus. Consistent with the sequence similarities, bbtRel was found to interact with a mammalian κB response element, to move into the nucleus when activated, and to be inhibited by the NF-κB-specific inhibitor helenalin. Similar to the other class I members, bbtp105 could be cleaved into the mature form p58. Such endoproteolysis depends on the GRR sequence and requires both protease degradation and caspase 8 cleavage. Furthermore, we found that bbtIκB and the unprocessed bbtp105 can inhibit the transcriptional activity of bbtRel, whereas bbtp58 forms homodimers or heterodimers with bbtRel to create a mature NF-κB complex. Finally, we found that the survival rate and the expression of bbtIκB and TNF-α-like genes were decreased when adult amphioxus were treated with helanalin before immune challenge, suggesting the archaic roles for NF-κB signaling in innate immune responses in a basal chordate. The presence of the NF-κB-IκB cascade in amphioxus indicates that it is a significant feature linking invertebrates to vertebrates and is refined in vertebrates through the expansion and divergence of genes involved in the cascade.
authors.affiliation: Department of Biochemistry, College of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People's Republic of China.
authors.forename: Shaochun
authors.initials: S
authors.lastname: Yuan
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.forename: Shengfeng
authors.initials: S
authors.lastname: Huang
authors.forename: Shangwu
authors.initials: S
authors.lastname: Chen
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002816:Chordata, Nonvertebrate; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007113:Immunity, Innate; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology; D045789:Sesquiterpenes, Guaiane; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; C001329:helenalin